Ciliary neurotrophic factor reduces the proliferation and promotes the differentiation of TH- MYCN transformed sympathoadrenal progenitors.

Abstract

Neuroblastoma is a childhood cancer caused by the transformation of sympathoadrenal progenitors. By following the formation of tumors in homozygous TH-MYCN mice, an established mouse model of neuroblastoma, we were able to capture transformed cells prior to the formation of large, vascularized tumors in order to determine the responsiveness of cells to neurotrophic factors. We discovered that the ciliary neurotrophic factor (CNTF) receptor is abundantly expressed in tumor cells from these mice. Furthermore, CNTF - but not nerve growth factor, brain-derived nerve growth factor, neurotrophin 3, or glial cell line-derived neurotrophic factor - promoted neuronal differentiation and withdrawal from the cell cycle. Thus, the transformation of sympathoadrenal progenitors by MYCN overexpression differentially affects responsiveness to neurotrophic molecules.